| 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. GRANDY, D.K., MARCHIONNI, M.A., MAKAM, H., STOFKO, R.E., ALFANO, M.,
FROTHINGHAM, L., FISCHER, J.B., BURKE-HOWIE, K.J., BUNZOW, J.R.,
SERVER, A.C. AND CIVELLI, O.
Cloning of the cDNA and gene for a human D2 dopamine receptor.
PROC.NATL.ACAD.SCI.U.S.A. 86 9762-9766 (1989).
7. WATSON, S. AND ARKINSTALL, S.
Dopamine.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp96-110.
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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].
Dopamine neurons in the vertebrate central nervous system are involved in
the initiation and execution of movement, the maintenance of emotional
stability, and the regulation of pituitary function [6]. Various human
neurological diseases (e.g., Parkinson disease and schizophrenia), are
believed to be manifestations of dopamine and dopamine receptor imbalance.
The receptors have been divided into several different subtypes (designated
D1-D5), which may be distinguished by their G protein coupling, ligand
specificity, anatomical distribution and physiological effects.
D2 receptors have a similar pharmacological profile to D3 and D4 receptors.
They are present in high levels in the principal dopamine projection areas
(including the caudate-putamen, nucleus accumbens and olfactory tubercle);
they are found in cell bodies of dopaminergic neurons in the substantia
nigra and ventral tegmental area; and, in the periphery, they are found in
the pituitary, heart and blood vessels [7].
DOPAMINED2R is a 6-element fingerprint that provides a signature for the
D2 family of dopamine receptors. The fingerprint was derived from an initial
alignment of 6 sequences: the motifs were drawn from conserved sections
within either loop or N-terminal regions, focusing on those areas of the
alignment that characterise the D2 receptors but distinguish them from the
rest of the rhodopsin-like superfamily - motif 1 lies at the N-terminus;
motifs 2-5 span the third cytoplasmic loop; and motif 6 spans the third
external loop. A single iteration on OWL28.1 was required to reach
convergence, no further sequences being identified beyond the starting set.
A single partial match was also found, D2D2_XENLA, a D2 receptor fragment
lacking the first motif.
An update on SPTR37_9f identified a true set of 6 sequences.
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