| 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.
Angiotensin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp55-59.
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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].
Angiotensin II is the principal mediator of the renin-angiotensin system;
it circulates in the bloodstream, stimulating vasoconstriction and
retention of salt and water [6]. It also stimulates increased fluid intake
and regulates the neuroendocrine system. Many of its actions are mediated
by release of hormones from endocrine glands, e.g. vasopressin, catechol-
amines, aldosterone, growth-hormone, etc.. Molecular cloning studies have
identifed 2 major receptor subtypes, designated AT1 and AT2.
The AT2 receptor is abundant in the adrenal medulla, uterus and brain [6].
Activation of AT2 receptors has been reported to decrease basal cGMP levels
and to inhibit atrial natriuretic peptide-stimulated formation of cGMP,
possibly by activation of a protein tyrosine phosphatase [6].
ANGIOTENSN2R is a 9-element fingerprint that provides a signature for AT2
angiotensin II receptors. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved sections
largely within loop or N- and C-terminal regions, focusing on those areas
of the alignment that characterise the AT2 receptors but distinguish them
from the rest of the angiotensin family - motifs 1 and 2 span the N-terminus;
motif 3 spans the first cytoplasmic loop; motif 4 spans the second
cytoplasmic loop, leading into TM domain 4; motifs 5 and 6 span the second
external loop; motif 7 lies in the third cytoplasmic loop; and motifs 8 and
9 span the C-terminus. A single iteration on OWL29.0 was required to reach
convergence, no further sequences being identified beyond the starting set.
A single partial match was also found, S81979, an ovine angtiotensin II
receptor fragment.
An update on SPTR37_9f identified a true set of 3 sequences.
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