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PR00640

Identifier
GASTRINRELPR  [View Relations]  [View Alignment]  
Accession
PR00640
No. of Motifs
6
Creation Date
08-DEC-1996  (UPDATE 07-JUN-1999)
Title
Gastrin-releasing peptide receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00358 BOMBESINR
INTERPRO; IPR001966
GCRDB; GCR_0096; GCR_0097; GCR_0187
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, S.
Bombesin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.60-66.

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].
 
Bombesins are peptide neurotransmitters whose biological activity resides
in a common C-terminal sequence, WAXGHXM [6]. In the periphery, bombesin-
related peptides stimulate smooth muscle and glandular secretion. In the
brain, these peptides are believed to play a role in homeostasis, thermo-
regulation and metabolism, and have been reported to elicit analgesia and
excessive grooming, together with central regulation of a variety of
peripheral effects. 
 
Mammalian bombesins are encoded by 2 genes. The preproGRP gene transcript
encodes a precursor of 147 amino acids, which gives GRP and GRP18-27. The
preproNMB gene transcript encodes a precursor of 117 amino acids, which is
metabolised to neuromedin B. Receptors for these peptides have widespread
distribution in peripheral tissue. High levels are found in smooth muscle
and in the brain. 
 
The gastrin-releasing peptide receptor has a wide distribution in peripheral
tissue [6]. High levels are found in smooth muscle (e.g., intestine, stomach
and bladder) and in secretory glands (e.g., pancreas). In the brain, it is
found in high levels in the hypothalamus, and is present in other areas in
lower levels (e.g., the olfactory tract, dendate gyrus and cortex) [6]. It
is also found in various cell lines (e.g., Swiss 3T3 fibroblasts and small-
cell lung carcinomas [6]). GRP receptors activate the phosphoinositide
pathway via a pertussis-toxin-insensitive G protein, probably of the Gq/G11
class [6].
 
GASTRINRELPR is a 6-element fingerprint that provides a signature for the
gastrin-releasing peptide receptors. The fingerprint was derived from an
initial alignment of 3 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 GRP receptors but distinguish
them from the rest of the bombesin family - motifs 1 and 2 lie at the
N-terminus; motif 3 lies in the second external loop; and motifs 4-6 span
the C-terminus. A single iteration on OWL29.0 was required to reach
convergence, no further sequences being identified beyond the starting set.
 
An update on SPTR37_9f identified a true set of 3 sequences.
Summary Information
3 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6333333
5000000
4000000
3000000
2000000
123456
True Positives
GRPR_HUMAN    GRPR_MOUSE    GRPR_RAT      
Sequence Titles
GRPR_HUMAN  Gastrin-releasing peptide receptor (GRP-R) (GRP-preferring bombesin receptor) - Homo sapiens (Human). 
GRPR_MOUSE Gastrin-releasing peptide receptor (GRP-R) (GRP-preferring bombesin receptor) - Mus musculus (Mouse).
GRPR_RAT Gastrin-releasing peptide receptor (GRP-R) (GRP-preferring bombesin receptor) - Rattus norvegicus (Rat).
Scan History
OWL29_0    1  50   NSINGLE    
SPTR37_9f 2 4 NSINGLE
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
NNCSHLNLEVDPFLSC GRPR_RAT 4 4 -
NNCSHLNLDVDPFLSC GRPR_MOUSE 4 4 -
NDCFLLNLEVDHFMHC GRPR_HUMAN 4 4 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CNNTFNQTLSPPKMD GRPR_RAT 19 -1 -
CNDTFNQSLSPPKMD GRPR_MOUSE 19 -1 -
CNISSHSADLPVNDD GRPR_HUMAN 19 -1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
DLHPFHVKDTNQ GRPR_RAT 181 147 -
DLHPFHVKDTNQ GRPR_MOUSE 181 147 -
DLHPFHEESTNQ GRPR_HUMAN 180 146 -

Motif 4 width=17
Element Seqn Id St Int Rpt
LLCCQPSLLNRSHSTGR GRPR_RAT 338 145 -
LLCCQPGLMNRSHSTGR GRPR_MOUSE 338 145 -
LLCCQPGLIIRSHSTGR GRPR_HUMAN 337 145 -

Motif 5 width=15
Element Seqn Id St Int Rpt
RSTTCMTSFKSTNPS GRPR_RAT 354 -1 -
RSTTCMTSFKSTNPS GRPR_MOUSE 354 -1 -
RSTTCMTSLKSTNPS GRPR_HUMAN 353 -1 -

Motif 6 width=15
Element Seqn Id St Int Rpt
ATFSLINGNICHEGY GRPR_RAT 369 0 -
ATFSLINRNICHEGY GRPR_MOUSE 369 0 -
ATFSLINGNICHERY GRPR_HUMAN 369 1 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
NNCSHLNLEVDPFLSC GRPR_RAT 4 4 -
NNCSHLNLDVDPFLSC GRPR_MOUSE 4 4 -
NDCFLLNLEVDHFMHC GRPR_HUMAN 4 4 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CNNTFNQTLSPPKMD GRPR_RAT 19 -1 -
CNDTFNQSLSPPKMD GRPR_MOUSE 19 -1 -
CNISSHSADLPVNDD GRPR_HUMAN 19 -1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
DLHPFHVKDTNQ GRPR_RAT 181 147 -
DLHPFHVKDTNQ GRPR_MOUSE 181 147 -
DLHPFHEESTNQ GRPR_HUMAN 180 146 -

Motif 4 width=17
Element Seqn Id St Int Rpt
LLCCQPSLLNRSHSTGR GRPR_RAT 338 145 -
LLCCQPGLMNRSHSTGR GRPR_MOUSE 338 145 -
LLCCQPGLIIRSHSTGR GRPR_HUMAN 337 145 -

Motif 5 width=15
Element Seqn Id St Int Rpt
RSTTCMTSFKSTNPS GRPR_RAT 354 -1 -
RSTTCMTSFKSTNPS GRPR_MOUSE 354 -1 -
RSTTCMTSLKSTNPS GRPR_HUMAN 353 -1 -

Motif 6 width=15
Element Seqn Id St Int Rpt
ATFSLINGNICHEGY GRPR_RAT 369 0 -
ATFSLINRNICHEGY GRPR_MOUSE 369 0 -
ATFSLINGNICHERY GRPR_HUMAN 369 1 -