| 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. HONDA, Z., NAKAMURA, M., MIKI, I., MINAMI, M., WATANABE, T., SEYAMA, Y.,
OKADO, H., TOH, H., ITO, K. AND MIYAMOTO, T.
Cloning by functional expression of platelet-activating factor receptor
from guinea-pig lung.
NATURE 349 342-346 (1991).
7. SEYFRIED, C.E., SCHWEICKART, V.L., GODISKA, R. AND GRAY, P.W.
The human platelet-activating factor receptor gene (PTAFR) contains no
introns and maps to chromosome 1.
GENOMICS 13 832-834 (1992).
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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].
Platelet-activating factor (PAF), a unique phospholipid mediator, possesses
potent proinflammatory, smooth-muscle contractile and hypotensive activities,
and appears to be crucial in the pathogenesis of bronchial asthma and in the
lethality of endotoxin and anaphylactic shock [6,7]. However, little is
known of the molecular properties of the PAF receptor and related signal
transduction systems [6]. The gene for the human PAF receptor (PAFR) has
been isolated, and encodes a protein that is highly similar to the guinea
pig PAF receptor. Analysis of somatic cell hybrids suggests that PAFR is
encoded by a single gene on human chromosome 1 [6].
PAFRECEPTOR is an 11-element fingerprint that provides a signature for the
platelet activating factor receptors. The fingerprint was derived from an
initial alignment of 4 sequences: the motifs were drawn from conserved
regions spanning the full alignment length, focusing on those sections
that characterise the PAF receptors but distinguish them from the rest of
the rhodopsin-like superfamily - motif 1 resides at the N-terminus; motifs 2
and 3 span the first cytoplasmic and external loops respectively; motif 4
spans the C-terminus of TM domain 3 and the second cytoplasmic loop; motif
5 spans the C-terminus of TM domain 4, leading into the second external
loop; motif 6 lies in the second external loop; motif 7 encodes the third
cytoplasmic loop; motif 8 lies at the C-terminus of TM domain 6; motif 9
lies at the N-terminus of TM domain 7; and motifs 10 and 11 reside at the
C-terminus. A single iteration on SPTR37_9f was required to reach convergence,
no further sequences being identified beyond the starting set.
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