| 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. EIDNE, K.A., ZABAVNIK, J., PETERS, T., YOSHIDA, S., ANDERSON, L.
AND TAYLOR, P.L.
Cloning, sequencing and tissue distribution of a candidate G protein-coupled
receptor from rat pituitary gland.
FEBS LETT. 292 243-248 (1991).
7. SONG, Z.H., MODI, W. AND BONNER, T.I.
Molecular cloning and chromosomal localization of human genes encoding
three closely related G protein-coupled receptors.
GENOMICS 28 347-349 (1995).
8. WATSON, S. AND ARKINSTALL,
Orphan receptors.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp223-230.
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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].
Several 7TM receptors have been cloned but their endogenous ligands are
unknown; these have been termed orphan receptors. A new GPCR, GPR12, was
isolated from a rat pituitary library, and is found in discrete regions
of the brain, pituitary and testis, but is absent in other tissues [6-8].
Three human homologues (GPR12, GPR6 and GPR3) have also been isolated [7].
The 3 genes have been localised to human chromosomal regions 13q12, 6q21
and 1p34.3-p36.1 respectively.
GPRORPHANR is an 8-element fingerprint that provides a signature for the
GPR family of orphan receptors. The fingerprint was derived from an
initial alignment of 8 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 GPR receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motif 1
lies at the N-terminus of TM domain 1; motif 2 spans the first cytoplasmic
loop; motif 3 spans the first external loop, leading into TM domain 3;
motif 4 lies in the second cytoplasmic loop; motifs 5 and 6 span the third
cytoplasmic loop; motif 7 spans the the third external loop, leading into
TM domain 7; and motif 8 resides at the C-terminus. A single iteration
on OWL29.0 was required to reach convergence, no further sequences being
identified beyond the starting set. Two partial matches were found: RATGPCRA
is an N-terminal fragment that matches motifs 1-3; and MSHR_BOVIN is a
melanocyte stimulating hormone receptor that matches motifs 4 and 8.
An update on SPTR37_9f identified a true set of 7 sequences.
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