| 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.
Neurotensin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994,
PP.199-201.
7. VINCENT, J-P., MAZELLA, J. AND KITABGI, P.
Neurotensin and neurotensin receptors.
TRENDS PHARMACOL.SCI. 20(7) 302-309 (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,
paracrine 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].
Neurotensin is a 13-residue peptide transmitter, sharing significant
similarity in its 6 C-terminal amino acids with several other neuropeptides,
including neuromedin N. This region is responsible for the biological
activity, the N-terminal portion having a modulatory role. Neurotensin is
distributed throughout the central nervous system, with highest levels in
the hypothalamus, amygdala and nucleus accumbens. It induces a variety of
effects, including: analgesia, hypothermia and increased locomotor activity.
It is also involved in regulation of dopamine pathways. In the periphery,
neurotensin is found in endocrine cells of the small intestine, where it
leads to secretion and smooth muscle contraction [6].
The existence of 2 neurotensin receptor subtypes, with differing affinities
for neurotensin and differing sensitivities to the antihistamine
levocabastine, was originally demonstrated by binding studies in rodent
brain. Two neurotensin receptors (NT1 and NT2) with such properties have
since been cloned and have been found to be G protein-coupled receptor
family members [7].
NEUROTENSINR is a 6-element fingerprint that provides a signature for the
neurotensin receptors. The fingerprint was derived from an initial alignment
of 6 sequences: the motifs were drawn from conserved sections within the N-
and C-termini and external loop regions, focusing on those areas of the
alignment that characterise the neurotensin receptors but distinguish them
from the rest of the rhodopsin-like superfamily - motif 1 resides at the
N-terminus, leading into TM domain 1; motifs 2 and 3 span the first external
loop; motifs 4 and 5 span the third external loop; and motif 6 resides at
the C-terminus. A single iteration on SPTR39_15f was required to reach
convergence, no further sequences being identified beyond the starting set.
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