| 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. YOKOTA, Y., SASAI, Y., TANAKA, K., FUJIWARA, T, TSUCHIDA, K.,
SHIGEMOTO, R., KAKIZUKA, A., OHKUBO, H. AND NAKANISHI, S.
Molecular characterisation of a functional cDNA for rat substance P
receptor.
J.BIOL.CHEM. 264(30) 17649-17652 (1989).
7. WATSON, S. AND ARKINSTALL, S.
Tachykinins.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.261-70.
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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 receptors are present in very small quantities in the cell
and are embedded tightly in the plasma membrane. The neuropeptides exhibit
a high degree of functional diversity through both regulation of peptide
production and through peptide-receptor interaction [6]. The mammalian
tachykinin system consists of 3 distinct peptides: substance P, substance
K and neuromedin K. All possess a common spectrum of biological activities,
including sensory transmission in the nervous system and contraction/
relaxation of peripheral smooth muscles, and each interacts with a
specific receptor type.
In the brain, high concentrations of the NK1 receptor are found in striatum,
olfactory bulb, dendate gyrus, locus coeruleus and spinal chord [7]. In
peripheral tissues NK1 receptors are found in smooth muscle (e.g., ileum
and bladder), enteric neurons, secretory glands (e.g., parotid), cells of
the immune system and vascular endothelium [7]. NK1 receptors activate the
phosphoinositide pathway through a pertussis-toxin-insensitive G protein [7].
NEUROKININ1R is a 9-element fingerprint that provides a signature for the
neurokinin NK1 receptors. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved sections
within either loop or TM regions, focusing on those areas of the alignment
that characterise the NK1 receptors but distinguish them from the rest of
the neurokinin family - motifs 1 and 2 reside at the N-terminus; motifs 3
and 4 span the second external loop; motif 5 spans the C-terminal portion of
TM domain 6 and the third external loop; and motifs 6-9 reside within the
C-terminus. Two iterations on OWL30.2 were required to reach convergence,
at which point at true set comprising 5 sequences was identified. A single
partial match was also found, NK1R_RANCA, an NK1 receptor from bull frog
that matches motifs 6, 8 and 9.
An update on SPTR37_9f identified a true set of 4 sequences, and 1
partial match.
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