| 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. MCKEE, K.K., PALYHA, O.C., FEIGHNER, S.D., HRENIUK, D.L., TAN, C.P.,
PHILLIPS, M.S., SMITH, R.G., VAN DER PLOEG, L.H. AND HOWARD, A.D.
Molecular analysis of rat pituitary and hypothalamic growth hormone
secretagogue receptors.
MOL.ENDOCRINOL. 11 415-423 (1997).
7. HOWARD, A.D., FEIGHNER, S.D., CULLY, D.F., ARENA, J.P., LIBERATOR, P.A.,
ROSENBLUM, C.I., HAMELIN, M., HRENIUK, D.L., PALYHA, O.C., ANDERSON, J.,
PARESS, P.S., DIAZ, C., CHOU, M., LIU, K.K., MCKEE, K.K., PONG, S.-S.,
CHAUNG, L.-Y., ELBRECHT, A., DASHKEVICZ, M., HEAVENS, R., RIGBY, M.,
SIRINATHSINGHJI, D.J.S., DEAN, D.C., MELILLO, D.G., PATCHETT, A.A.,
NARGUND, R., GRIFFIN, P.R., DEMARTINO, J.A., GUPTA, S.K., SCHAEFFER, J.M.,
SMITH, R.G. AND VAN DER PLOEG, L.H.T.
A receptor in pituitary and hypothalamus that functions in growth hormone
release.
SCIENCE 273 974-977 (1996).
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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].
Growth hormone (GH) release is thought to occur under the reciprocal
regulation of two hypothalamic peptides (GH releasing hormone (GHRH) and
somatostatin) via their engagement with specific cell surface receptors on
the anterior pituitary somatotroph [6,7]. GH-releasing peptides (such as
GHRP-6, and the nonpeptide mimetics, L-692, 429 and MK-0677) stimulate GH
release through their activation of a distinct receptor, the GH secretagogue
receptor (GHSR). This receptor couples to G-alpha-11 proteins.
GHSRECEPTOR is a 10-element fingerprint that provides a signature for the
growth hormone secretagogue type 1 receptors. The fingerprint was derived
from an initial alignment of 3 sequences: the motifs were drawn from
conserved sections within either loop or TM regions, focusing on those
areas of the alignment that characterise the growth hormone secretagogue
type 1 receptors but distinguish them from the rest of the rhodopsin-like
superfamily - motifs 1-3 span the N-terminal region, leading into TM domain
1; motif 4 encompasses part of the first external loop and TM domain 3;
motif 5 spans part of the second cytoplasmic loop and the N-terminal portion
of TM domain 4; motif 6 lies in the second cytoplasmic loop; motif 7
includes part of the second external loop and the N-terminus of TM domain 5;
motifs 8 and 9 spans the third cytoplasmic and third external loops
respectively; and motif 10 resides at the C-terminus. A single iteration on
SPTR37_10f was required to reach convergence, no further sequences being
identified beyond the starting set. Two partial matches were found: O93412
is an orphan GPCR from Sphoeroides nephelus that matches motifs 4, 7 and 9;
and GP38_HUMAN is a putative GPCR from Homo sapiens that matches motifs 3
and 4.
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