| 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,
Bradykinin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp67-70.
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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].
Bradykinins (BKs) are a family of short, structurally similar peptides that
activate sensory fibres, contract venous smooth muscle, stimulate release
of cytokines, induce connective tissue proliferation and mediate endo-
thelium-dependent vasodilation [6]. BK antagonists are of potential use
in the treatment of inflammation, asthma, mild pain and endotoxic shock.
BK receptors are widespread in peripheral tissues, and at least 3 different
receptor subtypes have been proposed. Of these, B2 is the predominant
subtype, mediating slow contraction of various smooth muscles (including
veins, intestine, uterus, trachea and lung), inducing endothelium-dependent
relaxation of arteries and arterioles, and stimulating natriuresis/diuresis
in kidney. BK also induces hyperalgesia through activation of B2 receptors
in sensory nerve fibres and dorsal root ganglion neurons [6].
BRADYKINNB2R is an 8-element fingerprint that provides a signature for
the B2 bradykinin receptors. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved sections
within either loop or TM regions, focusing on those areas of the alignment
that characterise the B2 bradykinin receptors but distinguish them from the
rest of the bradykinin receptor family - motif 1 lies at the N-terminus;
motifs 2 and 3 span the C-terminus of TM domain 4, leading into the second
external loop; motif 4 spans the third cytoplasmic loop; motif 5 lies in
the third external loop; and motifs 6-8 span the C-terminus. A single
iteration on OWL30.2 was required to reach convergence, no further sequences
being identified beyond the starting set.
An update on SPTR37_9f identified a true set of 5 sequences, and 1
partial match.
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