| 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).
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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,
distinguished by their G protein coupling, ligand specificity, anatomical
distribution and physiological effects.
DOPAMINER is a 5-element fingerprint that provides a signature for the
dopamine 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 dopamine receptors but distinguish them from the rest of
the rhodopsin-like superfamily. Two iterations on OWL23.2 were required
to reach convergence, at which point a true set comprising 17 sequences
was identified. Several partial matches were also found, most of which
are dopamine receptor fragments.
An update on SPTR37_9f identified a true set of 37 sequences, and 3
partial matches.
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