| 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. TAL, M., AMMAR, D.A., KARPUJ, M., KRIZHANOVSKY, V., NAIM, M.
AND THOMPSON, D.A.
A novel putative neuropeptide receptor expressed in neural tissue,
including sensory epithelia.
BIOCHEM.BIOPHYS.RES.COMMUN. 209 752-759 (1995).
7. AMES, R.S., SARAU, H.M., CHAMBERS, J.K., WILLETTE, R.N., AIYAR, N.V.,
ROMANIC, A.M., LOUDEN, C.S., FOLEY, J.J., SAUERMELCH, C.F., COATNEY, R.W.,
AO, Z., DISA, J., HOLMES, S.D., STADEL, J.M., MARTIN, J.D., LIU, W.S.,
GLOVER, G.I., WILSON, S., MCNULTY, D.E., ELLIS, C.E., ELSHOURBAGY, N.A.,
SHABON, U., TRILL, J.J., HAY, D.W., DOUGLAS, S.A. ET AL..
Human urotensin-II is a potent vasoconstrictor and agonist for the orphan
receptor GPR14.
NATURE 401 282-286 (1999).
8. OPGAARD, O.S., NOTHACKER, H.-P., EHLERT, F.J. AND KRAUSE, D.N.
Human urotensin II mediates vasoconstriction via an increase in inositol
phosphates.
EUR.J.PHARMACOL. 406 265-271 (2000).
9. DOUGLAS, S.A. AND OHLSTEIN, E.H.
Human urotensin-II, the most potent mammalian vasoconstrictor identified
to date, as a therapeutic target for the management of cardiovascular
disease.
TRENDS CARDIOVASC.MED. 10 229-237 (2000).
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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].
Urotensin II is a vasoactive `somatostatin-like' peptide, first identified
in fish spinal cord but later found in humans and other mammals [7]. A
cyclic hexapeptide region of the molecule is responsible for the biological
activity and is absolutely conserved between species [8]. Urotensin II is
the most potent mammalian vasoconstrictor identified to date and causes
contraction of arterial blood vessels, including the thoracic aorta [7,8].
The urotensin II receptor was originally isolated as an orphan receptor,
expressed in neural and sensory tissues and named GPR14, or sensory
epithelial neuropeptide-like receptor (SENR) [6]. The receptor has been
found to be expressed in the CNS (cerebellum and spinal cord), skeletal
muscle, pancreas, heart, endothelium and vascular smooth muscle [9]. It is
likely to be involved in the pathophysiological control of cardiovascular
function and may also influence CNS and endocrine functions [7,9]. Binding
of urotensin II to the receptor leads to activation of phospholipase C,
through coupling to Gq/11 family proteins [8]. The resulting increase in
intracellular calcium may cause the contraction of vascular smooth muscle
[8].
UROTENSIN2R is a 9-element fingerprint that provides a signature for the
urotensin II receptors. The fingerprint was derived from an initial
alignment of 2 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 urotensin II receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motifs
1-3 span the N-terminus; motif 4 spans the first external loop; motif 5
spans the second cytoplasmic loop; motif 6 lies in the second external
loop; motif 7 lies in the third cytoplasmic loop; motif 8 lies at the
C-terminus of TM domain 7; and motif 9 resides at the C-terminus. A single
iteration on SPTR39_15f was required to reach convergence, no further
sequences being identified beyond the starting set.
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