| 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).
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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.
NEUROKININR is an 8-element fingerprint that provides a signature for the
neurokinin receptors. The fingerprint was derived from an initial alignment
of 6 sequences: the motifs were drawn from conserved sections within either
loop or TM regions, focusing on those areas of the alignment that
characterise the neurokinin receptors but distinguish them from the
rest of the rhodopsin-like superfamily - motif 1 lies at the N-terminus
leading into TM domain 1; motif 2 spans the C-terminus of TM domain 1 and
part of the first cytoplasmic loop; motif 3 spans part of the first
external loop leading into TM domain 3; motif 4 lies in the second
cytoplasmic loop; motif 5 lies at the N-terminus of TM domain 5; motif 6
spans the C-terminus of TM domain 5 leading into the third cytoplasmic
loop; motif 7 spans part of the third external loop leading into TM domain
7; and motif 8 lies at the C-terminus. Two iterations on OWL23.2 were
required to reach convergence, at which point a true set comprising 16
sequences was identified. Several partial matches were also found, all
of which are neurokinin receptor fragments or close superfamily relatives.
An update on SPTR37_9f identified a true set of 15 sequences, and 5
partial matches.
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