| 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. WATSON, S. AND ARKINSTALL,
Orphan receptors.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp223-230.
7. RIMLAND, J., XIN, W., SWEETNAM, P., SAIJOH, K., NESTLER, E.J. AND
DUMAN, R.S.
Sequence and expression of a neuropeptide Y receptor cDNA.
MOL.PHARMACOL. 40 869-875 (1991).
8. JAZIN, E.E., YOO, H., BLOMQVIST, A.G., YEE, F., WENG, G., WALKER, M.W.,
SALON, J., LARHAMMAR, D. AND WAHLESTEDT, C.
A proposed bovine neuropeptide Y (NPY) receptor cDNA clone, or its human
homologue, confers neither NPY binding sites nor NPY responsiveness on
transfected cells.
REGUL.PEPT. 47 247-258 (1993).
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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. LCR1 was isolated from
a locus coeruleus library and its mRNA is also present in cerebellum, pons,
dorsal raphe, thalamus and substantia nigra [6,7]. It was originally thought
to encode a neuropeptide Y receptor (NPY3-R) [7], but this has been shown to
be incorrect [8], and it is now thought to be a type 4 C-X-C chemokine
receptor.
CXCCHMKINER4 is a 9-element fingerprint that provides a signature for
the type 4 C-X-C chemokine receptors. The fingerprint was derived from
an initial alignment of 6 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 type 4 C-X-C chemokine
receptors but distinguish them from the rest of the rhodopsin-like super-
family - motifs 1 and 2 span the N-terminus, motif 2 leading into the
N-terminal portion of TM domain 1; motif 3 spans the first cytoplasmic
loop; motif 4 spans the first external loop; motif 5 lies in the second
cytoplasmic loop; motif 6 lies in the second external loop; motif 7 spans
the third cytoplasmic loop; motif 8 spans the third external loop; and
motif 9 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. Several partial matches were also found: OAU38942 and
MMLCR11 are N-terminal fragments lacking the last 3 and the last 4 motifs
respectively; and the remaining matches are closely related members of the
rhodopsin superfamily, largely belonging to the chemokine and interleukin-8
receptor families.
An update on SPTR37_9f identified a true set of 12 sequences, and 19
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