| 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.
Endothelin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp111-116.
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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].
Endothelins play an important role in the regulation of the cardiovascular
system [6]. They are the most potent vasoconstrictors identified, they
stimulate cardiac contraction, regulate release of vasoactive substances,
and stimulate mitogenesis in blood vessels in primary culture. They also
stimulate contraction in almost all other smooth muscles (e.g., uterus,
bronchus, vas deferens, stomach) and stimulate secretion in several tissues
(e.g., kidney, liver and adrenals) [6]. Endothelin receptors have also been
found in the brain (e.g., in the cerebral cortex, cerebellum and glial
cells). Endothelins have been implicated in a variety of pathophysiological
conditions associated with stress [6].
The ETB receptors are thought to play a significant role in endothelium-
dependent vasodilation and a lesser role in vasoconstriction [6]. In the CNS,
the receptor has been found in the cerebral cortex, hippocampus, cerebellum
and astrocytes. ETB receptors activate the phosphoinositide pathway through
a pertussis-toxin-insensitive G protein, though some actions are pertussis-
sensitive [6].
ENDOTHELINBR is an 8-element fingerprint that provides a signature for
the endothelin-B receptors. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved sections
within either loop or N- and C-terminal regions, focusing on those areas
of the alignment that characterise the endothelin-B receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motifs
1-4 span the N-terminus; motifs 5 and 6 span the first and second external
loops res.; and motifs 7 and 8 lie at the C-terminus. A single iteration on
OWL28.1 was required to reach convergence, no further sequences being
identified beyond the starting set.
An update on SPTR37_9f identified a true set of 6 sequences, and 1
partial match.
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