| Literature References | 1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
2. ISHIHARA T., NAKAMURA S., KAZIRO, Y., TAKAHASHI, T., TAKAHASHI, K.
AND NAGATA, S.
Molecular cloning and expression of a cDNA encoding the secretin receptor.
EMBO J. 10 1635-1641 (1991).
3. LIN, H.Y., HARRIS, T.L., FLANNERY, M.S., ARUFFO, A., KAJI, E.H.,
GORN, A., KOLAKOWSKI, L.F., LODISH, H.F. AND GOLDRING, S.R.
Expression cloning of adenylate cyclase-coupled calcitonin receptor.
SCIENCE 254 1022-1024 (1991).
4. JUEPPNER, H., ABOU-SAMRA, A.-B., FREEMAN, M., KONG, X.F.,
SCHIPANI, E., RICHARDS, J., KOLALOWSKI, L.F., HOCK, J., POTTS, J.T.,
KRONENBERG, H.M. AND SEGRE, G.E.
A G protein linked receptor for parathyroid hormone and parathyroid
hormone-related peptide.
SCIENCE 254 1024-1026 (1991).
5. ISHIHARA, T., SHIGEMOTO, R., MORI, K., TAKAHASHI, K. AND NAGATA, S.
Functional expression and tissue distribution of a novel receptor for
vasoactive intestinal polypeptide.
NEURON 8(4) 811-819 (1992).
6. WATSON, S. AND ARKINSTALL, S.
Parathyroid hormone (PTH).
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.231-233.
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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 secretin-like GPCRs include secretin [2], calcitonin [3], parathyroid
hormone/parathyroid hormone-related peptides [4] and vasoactive intestinal
peptide [5], all of which activate adenylyl cyclase and the phosphatidyl-
inositol-calcium pathway. The amino acid sequences of the receptors contain
high proportions of hydrophobic residues grouped into 7 domains, in a manner
reminiscent of the rhodopsins and other receptors believed to interact with
G proteins. However, while a similar 3D framework has been proposed to
account for this, there is no significant sequence identity between these
families: the secretin-like receptors thus bear their own unique `7TM'
signature.
Parathyroid hormone (PTH) is involved in calcium homeostasis within the
body in combination with calcitonin and vitamin D [6]. PTH is released in
response to hypocalcaemia and stimulates a rise in blood calcium; the
converse is true for calcitonin. The principle targets for PTH are bone
and kidney. Antagonists at the PTH receptor are of potential clinical use
in the treatment of hyperparathyroidism and short-term hypercalcaemic
states. In addition to its presence in bone and kidney, the receptor is
found in lower levels in blood vessels, where it mediates vasodilation.
The principle second messenger pathway is activation of adenylyl cyclase
through Gs. In addition, PTH stimulates phosphoinositide metabolism on
the expressed receptor.
PTRHORMONER is a 6-element fingerprint that provides a signature for the
parathyroid hormone/parathyroid related peptide receptors. The fingerprint
was derived from an initial alignment of 4 sequences: the motifs were
drawn from conserved sections within either loop or TM regions, focusing
on those areas of the alignment that characterise the parathyroid hormone
receptors but distinguish them from the rest of the secretin-like family -
motifs 1 and 2 were drawn from the N-terminal region leading into the first
TM domain; motif 3 lies in the loop region preceding the third TM domain;
motif 4 spans the loop region leading into the seventh TM region; and
motifs 5 and 6 were drawn from the C-terminus. Two iterations on OWL25.2
were required to reach convergence, at which point a true set comprising
7 sequences was identified.
An update on SPTR37_9f identified a true set of 5 sequences.
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